delta7-allopregnene compounds



A'T-ALLOPREGNENE COMPOUNDS Carl Djerassi, Birmingham, lVIich., andGeorge Rosenkranz and Jesus Romo, MexicoCity, Mexico, assignors 'toSyntex S.A.,' Mexico City, 'Mexico, a corporation of Mexico No Drawing.Application September 14, 1954 Serial No. 456,048

17 Claims. (01. zoo-239.55)

The present invention relates to: cyclopentanophenanthrene compounds andprocess for producing the samescribed are believed to be of substantialpotential value as therapeutics per se andas intermediatesforbiochemical introduction of aC-llhydroxyl group.

In application of Rosenkranz, Romo and Djerassi,

Serial No. 191,942, filed October 24', 1950,-,now U.S.

. Patent No. 2,858,307, a process is disclosed for theproductionofrcertain novel steroidal sapogenin compounds unsaturated in the 9 11or additionally unsaturated inthe 5,6 and 9(11) positions. a

In application of Djerassi and Rosenkranz, Serial No. 191,943, jfi1edOctober 24, 1950, now abandoned, there is disclosed the production ofcertain novel N-allopregnan previously mentioned application.

In accordance with thepresent invention it has been discovered thatcompounds of the character described in applications Serial No. 191,942and Serial No. 191,943, when subjected to certain novel processes to behereinafter described in detail, give rise to the production of certainnovel A' -unsaturated steroids of the allopregnene series.

In accordance withthe present invention it has been discovered that whencompounds of the character of derivatives starting with certain of thecompounds of the produced certain novel compounds as A-a1lopregnatrien-3B-ol-20-one 3-acetate which may be selectivelyhydrogenated to a novel A -allopregnadien-3/3- .ol-ZQ-one 3-acetatewhich may also be prepared by another-method to be hereinafterdescribed. Further treatment of A aIIOpregnadien-Sfi-ol-ZObne 3-acetate,with .perphthalic acid producesan oxido compound wherein the oxidogroup is in the 9(11) positon and there is also present in the compounda double bond in the 7,8 position. The following equation illustratesthe unsaturated in the 7 ,8'positon, which may be additionally aforemenn Process! CH: CH;

,.\Perphthallo I i 8-0111 C 0 ass gns In the foregoing equation thestarting material, alon treatment with lithium ammonia gives the knowncortithough indicated as a sapogenin of the 22-iso series, may someintermediate allopregna'ne-3fi-ol-l1,20-dione. be of the22-normaljseries. In placeof the 3+hydr0xy Reduction of a compound suchas A' -allopreggroup the sapogenin starting material may alsobe-esterinadienrSfl-QI-ZO-One 3-acetate with lithium aluminum hyfiedwith a suitable lower fatty acid or an aromatic acid, dride produced anovel compound characterized by a such as bcnzoic acid, was to producethe corresponding hydroxy grouping which could be esterified to produceesters rather than the acetates. In practicing the above a noveldiester'of A"-3,20-diols of the pregnene series, in

process, the sapogenin starting material, as for example this particularcase the compoundhaving, in addition to M -22-isoallospirostadien-3p-01,was heated in a sealed theA doublebond a AW double bond. The reactiontube at a temperaturein theneighborhood of 200 C. 10' involved maybe'eireinplifie'd bythrfollowing equation:

CH: on:

' =0 CHOR i CH] Reduction Llthlum'aluminum hydride no" no with aceticanhydride for a substantial period of time, as In practicing the aboveprocess, "A1 (iv-allopregnadien. vforv example eight hours. The excessanhydride is then "3fJ-ol-2-0-one 3-acetate was dissolved in a suitablesolvent, hydrolyzed with water, the crude 'furostatrien produced such asether, 'and'reduced with lithium aluminum hydride is then extractedwitha suitable solvent, *such as ether, asfby' adding the ether solutionto a lithium aluminum washed ju'ntil neutral and evaporated to, dryness.The "hydride solution in ether dropwise. Thereafter thereacfurostatri'e'n'is thenoxidized by adding thereto an aqueous"tionmixture was refluxed for a short period of time, as "solution ofchromium trioxide and acetic acid over a for example ten minutes, andtheexcess re -agent decomperiod ofapproximately half an hour. Prior tothe'adpd'sedwitha dilute acid. The die] thus produced was dition of thechromium trioxide and acetic acid the then extracted with a suitablesolvent, such as ether,

iurostatrien is dissolved in a suitable solvent, such as evaporated and.recrystallized from a suitable solvent.

ethylene fdichloride acetic acid and water. When the The diacetatecouldthen be produced by refluxing the ,addition of the chromium trioxide andacetic acid is rsultant diol'with acetic anhydride and pyridine. In thefinished'the reaction mixture" is allowed to stand at room alternative,other lower fatty acids could be used, as for temperature forapproximately. two hours, water is then examplewprop'ionic acid or anaromatic acid, such as added and the product extracted with a suitablesolvent, 40 benzoic, utilized in the form of an anhydride to producesuch as ether. The ether. solution is evaporated to dry- ;thecorresponding diacylate. In the above equation, thereness and theresidue is then saponified by refluxing with ..fore,.R may be hydrogenor the residue of a suitable acid potassium bicarbonate inmethahol-water solution and "preferably a lower fattyacidor benzoicacid.

then reacylated with acetic anhydride and pyridine. The

These novel compounds. are important intermediates "crude product ispreferably purifiedby chromatography for the productionofc'ortisonesince treatment with an and elution with a suitable solvent,such as hexane aliphatic peracid followed by treatment with alkali asset benzene, to produce A #a;llopreghatrien-36-01-20- forth in Unitedstatesapplication Serial No. 226,534,

one 3 acetate. The trienalone c'tiuld then be hydrofiled May 15, 1951,now abandoned, produces therefrom genated in the presence of apalladium-on-charcoal A -allopregnen-3B,11m,20-triol-7-one. Thiscompound catalyst while dissolved in a suitable;- solvent, such as maythen be saturated by treatment with hydrogen in the ethyl acetate.Preferably the hydhogenation was perpresence of a palladium catalyst toprepare allogregnaneformed at room temperature andatmospheric pressure.3fl,lla,20-triol-7-one. Wolff-Kishner reduction of this The resultantproduct A -allopregnadien-Sfl-ol-ZO-one last compound will produceallopregnane-3B,11u,20-triol S-acetate could then be oxidized bydissolving the same in which can be oxidized toallogregnane-3,11,20-trione.

I a suitable solvent, such as ether, allowing the solution to The trionecan be selectively reduced with Raney nickel stand at room temperaturefor approximately "one 'day catalyst to givethe known cortisoneintermediate allopregwith a suitable aromatic peracid, suchasEjperphthalicor nane-3fl-ol-l h20-dione.

perbenzoic acid, preferably the peracids being dissolved The saiiiecompounds may also be produced by reducin a suitable solvent such asether. The resultant prodii'ct ing a corresponding A compound withlithium aluminum is 9a,l1a-oxido-A' -allopregnen-3fl-ol-20-one 3-acetatehydride and thereafter dehydrogenating the novel A"-3,20- which ontreatment with boron trifluoride gives A -allodiol or preferably thediestens thereof with mercuric pregnen-3fi-ol-1L20-dione 3-acetate."Thislast compound acetate in accordance with the following equation:

on, v on, on,

am I C=0 CHOR CHOR CH: s CH;

:Reduetion Lithium Mercuric i aluminum acetate hydride Y dehydrogenationACO I l i H Hydrogen peroxide Sodium hydroxide such as acetic or benzoicacid, to produce the corresponding diacetate or other diacylate.Thereafter the A' -allopregnen-3,8,20-diol diacetate thus produced couldbe dehydrogenated by dissolving the diacetate in a suitable solvent,such as chloroform and shaking the solution at room temperature forapproximately eighteen hours with mercuric acetate dissolved in aceticacid. The resultant prodreaction may be exemplified by the followingequation:

CH1 CH1 Reduction Lithium aluminum hydride A00 l I H The lithiumaluminum hydride reduction of the abovementioned compounds was carriedout in the same manner as previously described and the corresponding Aallopregnadien-3/3,20-diol-was produced. Reaction with a suitableanhydride in the presence of pyridine produced the correspondingdiacylates, i.e. reaction with a lower fatty acid anhydride or benzoicacid anhydride produced the 3,20 diacylates of lower fatty acids orbenzoic acids, as previously set forth. Further, selective saturation ofthe 16-double bond with hydrogen in the presence of a palladium catalystproduced the same A' -allopregnen- 3,3,20-diol previously referred to.

In addition to the novel epoxides previously set forth, :it has beenfound that oxidation as with hydrogen peroxide as sodium hydroxide, of Acompounds, produced the corresponding 1'6,l7ct-oxido d"-allopregiiencompounds. If the A compound thus oxidized did not have the A doublebond, dehydrogenation with mercuric acetate would produce thecorresponding 1, ,,l7a-oxido A allopregnadien compound. This reactionmay be illustrated by the following equation:

Mei-curic acetate In proceeding according to the above equation Aallopregnenolone acetate was dissolved in a suitable solvent, such asmethanol, cooled to just below room temperature, as for example 18 C.,and treated at that temperature by simultaneously dropping into thesolution a hydrogenperoxide solution, as for example thirty partshydrogen peroxide in water and a solution of sodium hydroxide in waterand methanol. The reaction mixture was then stirred for a substantialperiod of time, as for example one hour, and the mixture was thenallowed to stand while cooling,'as for example to 0 C. for approximatelytwelve-hours.;, The crude product obtained on dilution with water and.filtration was acylated with pyridine-acetic anhydride and thenrecrystallized from a suitable solvent, such as'methanoLto form16,17a-OXidO- A' -a1lopregnen-3fi-o1-20 one 3 ace'tate. The 3-acetatecould then be saponified, as with dilute potassium bicarbonate solutionin methanol, to form the corresponding 3-hydroxy oxido. Instead of usingacetic anhydride for acetyla-tion, other lower fatty acid anhydridescould be used, or the anhydride of benzoic acid, to form thecorresponding 3-acylate. There has, therefore, been prepared inaccordance with the above equation certain novel A16,l7u-oxido-allopregnens having a Zip-hydroxy group and/or thecorresponding 3-esters.

The mercuric acetate dehydrogenation of A' -allopregnen compounds whichmay be additionally unsaturated in the 5,6 position gives rise to thecorresponding A1901) compounds and in the specific case of the A'compounds in the presence of a suitable alkali metal hydroxide, suchadditionally unsaturated in the 5,6 position to the A the fol--lowingequationsz '8 In accordance with the present invention Oppenauerox idation'of A compounds of the character hereinbefore described, whichare additionally unsaturated in the 5,6 "position, produce thecorresponding,A 'ketones. Thus K v -55 Oppeiiauer'oilidation'of A-pregnadien-3B-ol-20-onepro- CH; 1 H: duce'd A -pregnadien-3,ZO-dione(7-dehydroprogester- =0 one). The following equation is illustrative ofthis re- CH: action:

Mereurlc was 10 CH; OH:

CH] CH; (i=0 :=0 R0 CH:

Oppenauer oxidation Mercurle H0 O=QJ acetate In practicing the aboveprocess the A compound, as R0 for example A -pregnadien-3p-ol-20-one wasdissolved in a-suitable solvent, such as toluene, dried by distilling onapor'tion' ofthelsolvent, and then refluxed with cyclohexanone andaluminum t-butoxide for a substantial period The methodabove-illustrated, therefore, represents anof time, as for example threehours. Ether was then other method for the {production of the A1961)p'regnaadded; the solution washed, steam distilled, and the residue"diens. In practicing t'hemethodabove illustrated a cornabstracted'withether. The crude product could then be poundyas for example *A-pregnadien-3B-ol-20-one 3- purified by chromatography to produce theketone A acetate is dehydrogenated 'by' dis'solving the same in a.pregnadien-3,20-dione. This compound is a useful 'suitable'solvent;-as- 'for eirample chloroform, and treated .progestationalhormone. Although the above method is th'rne rcuric acetate-find glacialacetic acid by-shaking illustrated with the A compounds,.it is believedgenerally e same at roomtemperature for' along-period of time,applicable to A compounds of the pregnene series proas fonexample'eighteen-hours; There'af terithe solution vi'dingthe'secompoundshavea'3-hydroxy grouping. producedis filteredym'ore chloroformis added, and'the Oxidative "degradation of certain M-allofurostadienacetone is removed byvvashing with water and a suitable 40 compounds hasbeen found in accordance with the pres- "barbonate. The -'solutionis-"then'dried and evaporated to -ent' invention to produce a novelintermediate. Thus produce the equivalent compounds additionallyunsatutreatment of A -allofurostadien-3,B,26-dio1 diacetate rated in the9,11 position. yielded the crystalline A'-allopregnen-3[3,16/8-diol-20-one The A -pregnatrien-3B-ol-20-one thusproduced 3-acetate 16-7-methyl-6-acetoxy valerate. Saponificamay beconverted to the corresponding A' -pregnadiention of this compound withbicarbonate produced the 3fi-ol-20-one previously referred to by mildselective hy- A -allopregnadienB-ol-ZO-one 3-acetate in good yield.drogenation using a Raney nickel catalyst. This process is illustratedby thc'following equation:

on, on;

CH; CHI CH:

, 0 0 CHOR CH: /CH:

OOCCHr-GHz-CH Chromium OHzOAc trioxide acetic l acid lReflux Potassiumbicarbonate ICE:

OH: a-o

A' -allopregnadien-3p-ol-20-one 3-acetate thus produced can beselectively "hydrogenated to .the correspondingA"-allopregnen-3fl-ol-20-one S-acetate, and this compound upon treatmentwith mercuric acetate gives the same A -allopregnadien-3p-oI-ZO-one3-acetate previously described. a

The following specific examples serve to illustrate the presentinvention but arenot intended to limit the same:

Example I I A'W -allopregnalrien-3/8-0l-20-dne 3 acetate.-A solution of'2.5 g. of A -22-isoallospirostadien-313- ol,prepared in accordance withExample IV, U.S. application Serial No. 191,942, in 8-cc. of aceticanhydride was heated in a sealed tube at 196 for eight hours. The excessanhydride was hydrolyzed with water, the crude furostatriene wasextracted with ether, washed until neutral, evaporated to dryness andthen oxidized by adding a;solution of 1.5 g. of chromium trioxide in 2cc. of water and 20 cc. of acetic acid over a period of one-half hour toa vigorously stirred solution of the furostatriene in 35 cc. of ethylenedichloride, 40 cc. of acetic acid and 15 cc. of water. After standing atroom temperature 'for two hours, water was added, theproduct extractedwith ether, evaporated to dryness, the residue saponified .by refluxingforthirty-five minutes with a solution of 2 .g..of potassium bicarbonatein 100 cc. of methanol and .15 cc. of water and then reacetylated withacetic anhydride and pyridine at room temperature. On chromatographingthe crude product on alumina and eluting with mixtures of hexane-benzene(8:2), there was obtained the desired trienolone A-allopregnatrien-3,8-01-20- one I i-acetate with a melting point of16l-l63 C. (after recrystallization from methanol), +l96, .ultravioletmaximum at 234 mu (log E 4.44). Catalytic hydrogenation withpalladium-onwcharcoal in ethyl acetate-solution at room temperature andatmospheric :pressure afforded A -al1opregnadien-3p-ol-ZO-one 3-acetate, identical in all respects with a sample prepared. by the methodof Example XI. 1

Example 11 A"-all0pregnen-3fi,20-diol.A solution of 4.0 g. of

A' -allopregnen-3fi-ol-20-one 3-acetate prepared in accordance withExample II of application Serial No. 191,- 943, in 50 cc. of ether wasadded dropwise to a solution of 2 g. of lithium aluminum hydride in 50cc. of ether. After refluxing for ten minutes, the excess reagent wasdecomposed with dilute acid, the diol, A' -allopregnen- 3)8,20-diol,extracted with ether, evaporated and recystallized from ether-pentane;melting point 179-180 C., (11); -2l.8. When refluxed for one hour withacetic anhydride and pyridine, there was obtained afterrecrystallization from methanol the diacetate of A'-allopregnen-3p,20-diol with a melting point of 104-106 C., a)... .2. I1, I

Example III A allopregnadien-jpg0-diol -(a) By lithium aluminum hydridereduction of A -all0pregnadien-3fl-ol- 20-0ne 3-ac'etate.--2 grams'ofthe dienolone acetate prodnot of Example I in 50 cc. of etherwas reducedwith 1 g. of lithium aluminum hydride in 50 cc. of ether according tothe procedure of Example II. Recrystallization from acetone gave thediol, A -allopregnadien-313,20- diol, with a melting point of 183-185C., +24.4, ultraviolet maxima at 236 mu (log E 4.28) and 242 mu (log E"4.33).

Acetylation with acetic anhydride-pyridine produced the diacetate with amelting point of 113-115 C. (after recrystallization from methanol),(11);, +23.5.

(b) By mercuric acetate dehydrogenation of A"-all0- pregnen-3fl,20-di0ldiacetate.A solution of l g. of the diacetate product of Example H in 25cc. of chloroform was shaken at room temperature for eighteen hours withdiene of Example I in 30 cc. of ether was allowed to stand at roomtemperature for twenty-four hours with 1.3

.mols of perphthalic acid (other peracids such as perbenzoic acid couldalso be used) in 40 cc. of ether. After washing with sodium carbonateand water, the solvent was evaporated and the residue passed through ashort column of alumina. The crystalline eluates showed no selectiveabsorption in the ultraviolet, but gave a yellowish color withtetranitromethane indicating the presence of one double bond. Theanalysis was in good agreement with that expected for a monoepoxide andthe compound 9a,1la-oxido-A' -allopregnene-3fl-ol-20-one 3-acetate had amelting point of 188190 C. (after recrystallization frommethanol-water), (a) -5.

Example V A' -m-allopregnadien-3fi,20-diol.The lithium aluminum hydridereduction of A i-allopregnadien-3fi-ol-20- one-3-acetate prepared inaccordance with Example I, application Serial No. 191,943, was carriedout as described in Example II in ether solution (15 minutes refluxing)and after recrystallization from ether-hexane afforded the above diolwith a melting point of -147" C., (00 +6.6. The substance showed noselective absorption in the ultraviolet.

Example VI l6,I7a-0xido-A -all0pregnen-3B-0l-20-one.A solution of 5.0 g.of A' -allopregnenolone acetate in 400 cc, of methanol was cooled to 18and treated at that temperature with stirring simultaneously from twodropping funnels with 10 cc. of 30% hydrogen peroxide and with asolution of 2.3 g. of sodium hydroxide in 10 cc. of water and 25 cc. ofmethanol. After stirring for an additional hour, the mixture was allowedto stand at 0 overnight. The product, obtained on dilution with waterand filtration, was acetylated with pyridine-acetic anhydride and thenrecrystallized from methanol. The 3-acetate of l6,17a-oxido-A-allopregnen-3fi-ol-20-one had a melting point of 153-155 C., (a) +282",and an ultraviolet absorption maximum at 270 mu (log E 1.90) typical ofan isolated carbonyl group. Saponification with dilute methanolicpotassium bicarbonate solution followed by recrystallization from diluteacetone afforded 16,17 oxido-A' ,a1lopregnene-3fi-ol-20-one with amelting point of 124126 C., (a) -|-28.8.

Example VII 16,17a-oxid0-A' -all0pregnadien-3B-0l-20-0ne 3-acetater-To asolution of 1 g. of the acetoxy oxide of Example VI in 25 cc. ofchloroform was added a solution of-2 g. of mercuric acetate in 40 cc. ofacetic acid at room temperature and the mixture was shaken for twentyhours. -After dilution with water, the product was exultraviolet maximum232 mu(log E 4.13) and 242 mu Example 3 VIII Apregnatrien-3;3-0l-20-0ne.-The dehydrogenation was carried'out in themanner set forth in Example accuse -II-I(b) with 3.7 g. of A-allopregnadienG/Bol-20-one 3-a'cetate prepared according to theprocedure of Example V of application Serial No. 191,943, 8.0 g. of C.P.mercuric acetate, 150 cc. of acetic acid and 100 cc. of chloroform foreighteen hours. Crystallization from methanol yielded 1.44 g. (39%) of A-pregnatrien-3B-ol-20-one 3-aeetate with a melting point of l43-145(Kofier), unchanged on further recrystallization; (11); +323.9,ultraviolet maxima at 310 mu (log E 4.23 324 mu (log E 4.27) and 338 mu(log E 4.07).

Analysis.-Calculated for (3 1-1 C, 77.93; H, 8.53. Found: C, 77.57; H,8.38.

A -pregnatrien-3fi ol-20 one having a melting point of 201-203?(Kofler), (00 +2845 was obtained on 'saponification ofth'e above acetateand recrystallization from acetone.

Analysis-Calculated forC H O i C, 80.73; H, 9.03. Found: C, 80.65; H,9.14.

Example IX I A 'pregnatrien-3, 20-di0ne (7-dehydr0progesterone).--A'solution of 1.0 g. of A -pregnadien-3fl-ol-20-one in 170 cc. oftoluene was dried by distilling 20 'cc., and

was then refluxed for three hours with 25 cc. of cyclo- 'hexanone and2.0 g. of aluminum t-butoxide. After addition of some ether, thesolution was washed with water, Rochelle salt solution, and again withwater, steam distilled and the residue extracted with ether.Chromatography of the crude product on 25 g. of ethyl acetatewashedalumina and elution with hexane-benzene (1:1)

afforded the desired ketone in about 40% yield with a melting point of106-108 C., (a) +102", ultraviolet maximum at 238 mu (log E 4.29).

Analysr's.-Calculated for C H O C, 80.73; H, 9.03. Found: C, 80.46; H,9.25.

Example X A "-allopregnaaien-3B-0l-2O-one 3-acetate.A solution of 100 g.of A'l-22-isoallospirosten-3B-ol 3-acetate', prepared in accordance withapplication Serial No. 191,- 942, in 500 cc. of acetic anhydride washeated in a stainless steel autoclave for'eight hours at 196 C. and thenpoured into ice-cold water. After allowing the excess aceticanhydride't'o hydrolyze, theoily. acetate was ex- .tracted with ether,washed well with water and bicarbonate, dried and evaporated. In oneexperiment, a

small amount of the acetate was saponifie'd by boiling treated withstirring at 15 over a period of one-half hour with a solution of 60g. ofchromium trioxide in '80 cc. of water and 800 cc. of acetic acid. After2 hours at room temperature, water was added and the mixture wasextracted with chloroform, washed water and bicarbonate solution, driedand evaporated. Crystallization from methanol yielded 35 g. (30%) of A''-allopregnen-3B,16,3-diol-20-one 3-ac'etate 16-'y-methyl-6=acet-'oxyvalerate with a melting point of 104107 C; Further recrystallizationfrom methanol raised the melting point of the colorless crystals to113.5-115.5 C. (Kofler), (00 0, ultraviolet maximum at 276 mu (log 'E1.62).

Analysis-Calculated for C31H45O|1Z C, 70.16; H, 8.74. Found: C, 70.11;H, 8.87.

The filtrate was evaporated to dryness and the residue was refluxed forthirty-five minutes with a solution of 80 g. of potassium bicarbonate in180 cc. of water and 1.5 liters of methanol. Dilution with water,extraction with .ether, vreacetylation of the product with aceticanhydride 2. mixture in pyridine solution (1 hour, followedbycrystallization from methanol gave 7.3 g. of A' -allopregnadienj- 3fi-ol-20-one 3-'acetate with a melting point of 136- 1139 C.Chromatography of the mother liquors afiorded an additional 8.5 g. ofdie'noloneacetate with a melting point of 134-138 C. Since similarsaponification of the ester, A' -allop'regnen-3fi,l6fl-diol-20-one3-acetate 16-y-methylfi-acetoxyvalerate, gives between 8090% ofdienolone, the total yield of A -allopregnadien-3B-o1-20-one 3- acetateis 44-47% based on the original spirosten. The analytical sample was,obtained by recrystallization from methanol as colorlesscrystals with amelting point of .147 C. (Kofler), (00 +58, ultraviolet maximum at23 mu(logE4.11).

Analysis.-Calculated for C H O C, 77.49; H, 9.05. Found: C, 77.71; H,8.79.

Example XI A -all0pregnadieh 3 3-ol-20-one.-Tne mercuric acetatetreatment of A"-allopregnadien-3/3-ol-20-one 3-acetate, prepared inaccordance with Example III of application Seria'l. No; 191,943, wascarried out exactly as described in Example III(b) .and led in 58% yieldto A -allopregnadien-3{3*ol-20-one 3-acetate, which afterrecrystallization from methanol exhibited a melting point of -139141 C.(Kofler), (00 +789, ultraviolet maxima at 236 mu (log E 4.00) and 242 mu(log E 4.03).

abandoned.

We claim: l. A A7301) compound of the allopregnene series having thefollowing structural formula:

l no having the following structural formulas:

CHI

. =0 CH: L

wherein R is selected from the group consi ting of hy- 15 drogen, theresidue of a lower fatty acid and the residue 16.-allopregnadiene-3-ol-20-one of the formula cm on,

on. on. 41-0 o=o CH3 Ian-' I I R0 3 I 110 wherein R is a lower fattyacid radical.

l7. 9a,11a-oxido-A -allopregnene-3B-ol-20-one 3 ace- Kate.

of benzoic acid.

methyl-E-acetoxyvalerate.

A -allopregnen-318,20-diol. A -allopregnen-3fl,20-diol diacetate. A-a1lopregnadien-3 5,20-diol. A -allopregnatriene-3fi-ol-20-one3-acetate. A -pregnadien-3,2O-dione.

References Cited in the file of this patent UNITED STATES PATENTS MarkerMay 13, 1947 Mofiett May 6, 1952 Chemerda Feb. 14, 1956 FOREIGN PATENTSFrance Sept. 30, 1953 OTHER REFERENCES Djerassi: Jour. Org. Chem. 16,754- (1951). Rome: Jour. Am. Chem. Soc. 73, 5489- (1951). Fieser andFieser: Natural Products Related to Phenanthrene, 3rd edition (1949),pages 174; 188-9; 3 226-231; 251; 389; 410; 590.

1. A$7,9(11) COMPOUND OF THE ALLOPREGNENE SERIES HAVING THE FOLLOWINGSTRUCTURAL FORMULA:
 4. A 16,17A-OXIDO-$7 COMPOUND OF THE ALLOPREGENESERIES SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS HAVING THEFOLLOWING STRUCTURAL FORMULAS: